Muthu Periasamy, Ph.D.

Professor
Chair, Department of Physiology and Cell Biology
Associate Director, Davis Heart & Lung Research Institute

300 Hamilton Hall
1645 Neil Avenue
Columbus OH 43210-1218

614-292-2310 (office)
614-292-4888 (fax)
periasamy.1@osu.edu

Education:
Ph.D., Biochemistry and Molecular Biology, University of Montpellier, Monpellier-Cedex, France (1976-1980)
Postdoctoral Training: Albert Einstein College of Medicine (1980-1982); Harvard Medical School, Boston (1982-1985)

Research Description:
Dr. Periasamy is Professor and Chair of the Department of Physiology and Cell Biology and Associate Director of the Davis Heart and Lung Research Institute. His research expertise includes biochemistry, molecular genetics and Physiology. Much of his early education was in India and he received a M.Phil degree in Life Sciences from Jawaharlal Nehru University, New Delhi (1975). A fellowship from the Government of France allowed him to complete his Ph.D. thesis in Biochemistry at the University de Montpellier, France in 1979. Subsequently he did postdoctoral research at Albert Einstein College of Medicine (NY) and Harvard Medical School (Boston) (1980-1985). During his postdoctoral research he specialized in molecular genetics of the heart. He and his colleagues were responsible for applying molecular genetics tools to identify cardiac muscle specific genes. These pioneering studies led to the foundation of a whole new field, namely molecular cardiology. Following his postdoctoral research he served as Assistant Professor in the Department of Molecular Physiology and Biophysics at the University of Vermont (1986-1992) and as Associate Professor and Professor at the University of Cincinnati (1992-2001).

Ongoing Research Projects:

The physiological relevance of Phospholamban and Sarcolipin: two small regulatory proteins that regulate SERCA pump activity in heart and skeletal muscle.
Muscle as a thermogenic organ: Sarcolipin regulation of the SERCA pump contributes to muscle thermogenesis and metabolism.
The role of altered SR-Calcium transport in heart failure: mechanisms contributing to RyR1 mediated calcium leak.

Dr. Periasamy’s research has been supported by grant awards from the National Institutes of Health and the American Heart Association since establishing his independent laboratory in 1986. He was recognized as an Established Investigator of the National American Heart Association in 1988. Currently, Dr. Periasamy serves on multiple leadership and review committees for the American Heart Association and National Institutes of Health on an Ad Hoc basis. He has authored over 175 peer-reviewed articles and served on editorial boards for several journals including Circulation Research, the American Journal of Physiology (Heart and Circulatory Physiology), Japanese Heart Journal, and the Journal of Molecular and Cellular Cardiology.

Techniques Available:

The laboratory uses a variety of techniques including gene cloning, site directed mutagenesis, adenoviral gene transfer into live cells, confocal imaging, electron microscopy, protein expression and protein biochemistry. We also carry out functional studies on isolated cardiac myocytes to determine myocyte contractility and calcium handling as well as isolated whole heart function studies. We also generate transgenic and knockout mouse models with altered levels of key calcium handling proteins including SR Ca²⁺ ATPase, Sarcolipin, Phospholamban and Calsequestrin. These genetically altered models are used to study how a mutation or loss of a protein affects Ca²⁺transport and overall cardiac function.

Current Research Support:

- NIH/NHLBI-R01 HL 088555 (01/01/2008-12/31/2013), Mechanisms regulating SR- Ca²⁺ ATPase in the Atria.

PI: Muthu Periasamy, Ph.D.

- NIH/NIAMD-R01 AR 064747-01 (07/01/2013-06/31/2018), Skeletal muscle, an important site of non-shivering thermogenesis.

PI: Muthu Periasamy, Ph.D. (Pending)

Sponsor/Mentor:

- AHA - Postdoctoral fellowship –Anuradha Kalyanasundaram PhD, 2013-2014 (Ohio Affiliate)

- ADA - Predoctoral fellowship – Joseph Ostler (MD, PhD student) , 2011-2014 (American Diabetes Association)

- AHA - Postdoctoral fellowship –Naresh Bal PhD, 2010-2012 (Ohio Affiliate)

- NIH T32 training grant for IBGP Graduate Students. PI: Ginny Saunders

- T32 Training grant in Congenital and Acquired Heart Disease. PI: Terry Elton and Pamela Lucchesi

Selected Publications:

1. Nagai R, Herzberg AZ, Brandl CJ, Fuji J, Tada M, MacLennan DH, Alpert NR, Periasamy M. Regulated expression of myocardial SR Ca2+ ATPase and phospholamban in response to pressure overload and thyroid hormone. Proc. Natl. Acad. Sci., USA 86:2966-2970, 1989.

2. Zarain-Herzberg A, Maclennan DH, Periasamy M. Characterization of rabbit cardiac sarco(endo)plasmic reticulum Ca2+ ATPase gene. J. Biol. Chem. 17:7723-7734, 1990.

3. Arai M, Otsu K, MacLennan DH, Alpert NR, Periasamy M. Effect of thyroid hormone on the expression of mRNA encoding sarcoplasmic reticulum proteins. Circ. Res. 69:266-276, 1991.

4. Arai M, Matsui H, Periasamy M. Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure. Circ. Res. 74:555-564, 1994.

5. Loukianov E, Ji Y, Grupp IL, Baker DL, Loukianova T, Grupp G, Lytton J, and Periasamy M. Enhanced myocardial performance and increased Ca2+ transport function in transgenic hearts expression the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase. Circ. Res. 83:889-897, 1998.

6. Periasamy M, Reed TD, Liu LH, Ji Y, Loukianov E, Paul RJ, Nieman ML, Miller ML, Riddle T, Duffy JJ, Doetschman T, Norenz JN, and Shull GE. Impaired cardiac performance in heterozygous mice with a null mutation in sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) gene. J. Biol. Chem. 274:2556-2562, 1999.

7. M. Jane Lalli, Ji Yong, Katsuji Hashimoto, Gopal J. Babu, Darryl Kirkpatrick, Evgenij Loukianov, Richard A. Walsh, Mark Sussman, Eduardo Marban, Periasamy M. SERCA1a Structurally Substitutes for SERCA2a in the Cardiac Sarcoplasmic Reticulum and Increases Cardiac Ca2+ Handling Capacity. Circulation Research 89(2):160-7, 2001.

8. Periasamy M and Huke S. SERCA pump is a critical determinant of Ca2+ homeostasis and cardiac contractility. J. Mol. Cell Cardiol. 33:1053-1063, 2001.

9. Babu GJ, Bhupathy P, Petrashevskaya NN, Janssen PM, Ziolo MT, Periasamy M. Targeted overexpression of sarcolipin in the mouse heart decreases sarcoplasmic reticulum calcium transport and cardiac contractility J Biol Chem. Feb 17;281(7):3972-9, 2006.

10. Babu GJ, Bhupathy P, Timofeyev V, Petrashevskaya NN, Reiser PJ, Chiamvimonvat N, Periasamy M. Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility. Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17867-72.

11. Periasamy M, Bhupathy P, Babu GJ. Regulation of sarcoplasmic reticulum Ca2+ ATPase pump expression and its relevance to cardiac muscle physiology and pathology. Cardiovasc Res. 2008 Feb 1;77(2):265-73.

12. Chi M, Zhou Y, Vedamoorthyrao S, Babu GJ, Periasamy M. Ablation of smooth muscle myosin heavy chain SM2 increases smooth muscle contraction and results in postnatal death in mice. Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18614-8.

13. Periasamy M, Kalyanasundaram A. SERCA2a gene therapy for heart failure: ready for primetime? Mol Ther. 2008 Jun;16(6):1002

14. Periasamy M, Janssen PM. Molecular basis of diastolic dysfunction. Heart Fail Clin. 2008 Jan;4(1):13-21.

15. Stevens SC, Terentyev D, Kalyanasundaram A, Periasamy M, Györke S. Intra-sarcoplasmic reticulum Ca2+ oscillations are driven by dynamic regulation of ryanodine receptor function by luminal Ca2+ in cardiomyocytes. J Physiol. 2009 Oct 15;587(Pt 20):4863-72.

16. Sulaiman M, Matta MJ, Sunderesan NR, Gupta MP, Periasamy M, Gupta M Resveratrol, an activator of SIRT1, upregulates sarcoplasmic calcium ATPase and improves cardiac function in diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol. 2010 Mar;298(3):H833-43.

17. Bal NC, Sharon A, Gupta SC, Jena N, Shaikh S, Gyorke S, Periasamy M. The catecholaminergic polymorphic ventricular tachycardia mutation R33Q disrupts the N-terminal structural motif that regulates reversible calsequestrin polymerization..J Biol Chem. 2010 May 28;285(22):17188-96.

18. Bal NC, Jena N, Sopariwala D, Balaraju T, Shaikh S, Bal C, Sharon A, Gyorke S, Periasamy M. Probing cationic selectivity of cardiac calsequestrin and its CPVT mutants. Biochem J. 2011 Apr 15;435(2):391-9

19. Kalyanasundaram A, Bal NC, Franzini Armstrong C, Knollmann BC, Periasamy M. The calsequestrin mutation CASQ2D307H does not affect protein stability and targeting to the JSR but compromises its dynamic regulation of calcium buffering. J Biol Chem. 2010 Jan 29;285(5):3076-83

20. Gaburjakova M, Bal NC, Gaburjakova J, Periasamy M. Functional interaction between calsequestrin and ryanodine receptor in the heart. Cell Mol Life Sci. 2012 Oct 30.

21. Kalyanasundaram A, Viatchenko-Karpinski S, Belevych AE, Lacombe VA, Hwang HS, Knollmann BC, Gyorke S, Periasamy M. Functional consequences of stably expressing a mutant calsequestrin (CASQ2D307H) in the CASQ2 null background. Am J Physiol Heart Circ Physiol. 2012 Jan 1;302(1): H253-61. Epub 2011 Oct 7.

22. Bal NC, Maurya SK, Sopariwala DH, Sahoo SK, Gupta SC, Shaikh SA, Pant M, Rowland LA, Goonasekera SA, Molkentin JD, Periasamy M. Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals. Nat Med. 2012 Dec 6;18(12):1857.

23. Kalyanasundaram A, Lacombe VA, Belevych AE, Brunello L, Carnes CA, Janssen PM, Knollmann BC, Periasamy M, Gyørke S. Up-regulation of sarcoplasmic reticulum Ca2+ uptake leads to cardiac hypertrophy, contractile dysfunction and early mortality in mice deficient in CASQ2. Cardiovasc Res. 2012 Dec 4.